Project Summary/Abstract The goal of this project is to investigate, in parallel, the clinical efficacy and cost-effectiveness of combining aerobic exercise with repetitive task practice (RTP) to improve upper extremity motor recovery in individuals with stroke compared to time-matched RTP. Current approaches to stroke rehabilitation involve time-intensive, therapist-directed task practice that, while efficacious, are not easily translatable into the clinical setting, in part due to managed care reimbursement models that cap rehabilitation. The identification of a safe and cost- effective approach, such as aerobic exercise, to facilitate neuroplasticity post-stroke would optimize motor recovery while reducing costs associated with intensive rehabilitation. Our novel approach to stroke rehabilitation exploits the physiologic effects of intensive aerobic exercise training and combines it with an abbreviated session of motor task practice to improve motor recovery. This application of aerobic exercise training paired with RTP has been shown in our preliminary study (NIH R03HD073566) to enhance motor recovery greater than time-matched RTP without an aerobic exercise component. Results from our R03 indicated that those completing an 8-week high-rate aerobic exercise intervention paired with an abbreviated session of RTP exhibited an 8-point or 26% improvement in Fugl-Meyer scores at end of treatment despite completing 40% fewer RTP repetitions than the control group (time-matched RTP), that achieved a 17% improvement in Fugl-Meyer scores. The combined approach is expected to be more cost-effective, given that decreased one-on-one time is required, and clinical outcomes were superior in our preliminary study. Improvements in cardiovascular fitness and lower extremity motor function were also evident in the aerobic exercise group, indicating that the economic impact may extend beyond simply improving upper extremity function, and has the potential to reduce disability and diminish indirect costs associated with stroke. Positive results from our preliminary trial provide rationale for a systematic and larger scale trial to determine the clinical efficacy and cost effectiveness of aerobic exercise in facilitating motor recovery following stroke. A total of 60 individuals with chronic stroke will be randomized into one of two groups: 1) aerobic exercise and RTP or 2) time-matched RTP only. Both groups will receive an identical dose of contact time over 8 weeks (3X per week). Clinical and biomechanical outcomes measuring change in upper extremity motor function and quality of life metrics will be obtained, in addition to extensive participant demographics, and incorporated into decision analytic models to determine the incremental cost-effectiveness of each intervention. These analyses will examine cost-effectiveness in the short and long term from the healthcare provider and patient perspective, and identify specific social determinants of health that impact the cost-effectiveness of the interventions. Investigating and reporting the cost-effectiveness of each intervention represents a forward thinking approach, as emphasis in medicine and rehabilitation progress toward models emphasizing value over volume.